The central focus of research efforts outlined here is apolipopritein (B), the major polypeptide of human serum low density lipoprotein (LDL) and a component of very low density lipoproteins (VLDL) and chylomicra. The specific aims of the proposed research are to: 1) examine the extent of structural heterogeneity in VLDL and LDL utilizing sensitive immunological assays; 2) precisely define antigenic determinants of apo B present on chylomicra, VLDL, and LDL, and correlate their expression with lipoprotein functional properties; 3) study how the lipid composition of lipoprotein particles containing apo B modulates the expression of these determinants; and 4) obtain detailed information on the molecular structure of apo B. Several experimental methodologies described in this proposal are unique, most notably: 1) the production of monoclonal antibodies to apo B determinants expressed on chylomicra, VLDL, and LDL; 2) the use of an enzyme-linked immunosorbant assay (ELISA) to measure lipoprotein subpopulations; and 3) the ability to reconstitute apo B with defined lipids, allowing a systematic study of lipoprotein composition on the expression of important determinants on apo B. To summarize, the proposed experiments will provide basic as well as clinically relevant information. Fundamental questions concerning the structure of apo B, its disposition in lipoprotein particles, and how critical determinants on apo B specify the receptor mediated catabolism of lipoproteins will be addressed. Moreover, experiments designed to define and measure subpopulations of lipoproteins using extremely sensitive and specific immunological assays are proposed. As abberant populations of lipoproteins have been implicated in atherosclerosis, these experiments potentially afford ways of quickly delineating atherosclerotic risk in individuals, utilizing techniques heretofore unavailable.